Phencyclidine (PCP) is a powerful psychomimetic substance that produces psychopathological effects that mimic the primary symptoms of schizophrenia. The purpose of these studies was to define the actions of noncompetitive glutamate blockers such as MK-801 and PCP on basal ganglia functions. We have found that microinjectios of MK-801 and amphetamine into the n. accumbens produced profound increases in locomotor activity. The effects of amphetamine were dependent upon intact dopamine function while the effect of MK-801 were not. Injections of MK-801 into the medial thalamus, globus pallidus, subthalamic nucleus and ventral tegmental area also increased locomotor output in rats. Ibotenic acid lesions of the ventral pallium decreased the ability of MK- 801 but not amphetamine to increase locomotor activity. Systemic injections of amphetamine decreased extracellular GABA in the globus pallidus while MK-801 had no effect. MK-801 was found to induce C-fos in the medial thalamic nucleic and deep layers of all neocortical regions. Taken together, these findings suggest that fundamentally differed neural mechanism underlie the locomotor stimulatory effect of glutamate antagonists and sympathomimetic psychomotor stimulants.